Hippocampal Galectin-3 knockdown alleviates lipopolysaccharide-induced neurotoxicity and cognitive deficits by inhibiting TLR4/NF-кB signaling in aged mice.

doi:10.1016/j.ejphar.2022.175360

科研成果详情

题名	Hippocampal Galectin-3 knockdown alleviates lipopolysaccharide-induced neurotoxicity and cognitive deficits by inhibiting TLR4/NF-кB signaling in aged mice.
作者	Chen, Fang 1; Wu, Xiaofeng 1; Yang, Jiayong 1; Yu, Xuben2; Liu, Bili 1; Yan, Zhiwen 1
发表日期	2022-12-05
发表期刊	European journal of pharmacology 影响因子和分区
语种	英语
原始文献类型	Journal Article ; Article
关键词	Alzheimer's disease Cognitive deficits Galectin-3 Lipopolysaccharide Neuroinflammation Alzheimer?s disease
其他关键词	ALZHEIMERS-DISEASE ; ACTIVATION ; MEMORY ; BRAIN ; MODEL ; PROLIFERATION ; INFLAMMATION ; IMPAIRMENT
摘要	Neuroinflammation is thought to contribute to the onset and progression of Alzheimer's disease (AD). Galectin-3 (Gal-3), the only member of the galectin chimeric subfamily, is a key regulator of neuroinflammation and microglial activation. However, the effects of Gal-3 inhibition in AD-related neuroinflammation are unclear. Here, we investigated whether hippocampal Gal-3 knockdown alleviated lipopolysaccharide (LPS)-induced neurotoxicity and cognitive deficits, as well as the underlying mechanisms. First, we bilaterally injected aged mice (23 months old) with anti-Gal-3 short hairpin RNA into the hippocampus dentate gyrus, followed by systemic LPS administration. To determine the effects of hippocampal Gal-3 knockdown on neuroinflammatory response and neuronal apoptosis, we assessed the effects of Gal-3 silencing on the levels of pro-inflammatory cytokines, microglial activation, and apoptosis in the hippocampus of LPS-exposed aged mice. Behavioral tests were used to access the cognitive function of the mice. To explore the potential signaling, protein extracts from the brains of mice were subjected to analyze the expression levels of key molecules (including Toll-like receptor 4 (TLR4), myeloid differentiation factor 88, and nuclear transcription factor-κB (NF-κB) p65) of the TLR4/NF-кB pathway, and BV2 cells were pretreated with TLR4 inhibitor or NF-κB inhibitor before Gal-3 stimulation. These analyses showed that hippocampal Gal-3 knockdown attenuated neuroinflammation and neuronal apoptosis in the hippocampus of LPS-challenged aged mice, and this was associated with improved cognitive function. Hippocampal Gal-3 knockdown may protect against LPS-induced neurotoxicity by inhibiting the TLR4/NF-кB pathway. Our findings highlight Gal-3 as a potential therapeutic target against AD-associated neuroinflammation.
资助项目	National Natural Science Foundation of China; Natural Science Foundation of Fujian Province; Natural Science Foundation of Zhejiang Province; Training Program for Key Talents of Fujian Provincial Health Commission; Xiamen Key Laboratory of Pharmacodynamics Studies of Traditional Chinese Medicine; [81903585]; [82104145]; [2020D031]; [LQ20H310003]; [2020GGB053]
出版者	ELSEVIER
出版地	AMSTERDAM
ISSN	0014-2999
EISSN	1879-0712
卷号	936 页码:175360
DOI	10.1016/j.ejphar.2022.175360
页数	14
WOS类目	Pharmacology & Pharmacy
WOS研究方向	Pharmacology & Pharmacy
WOS记录号	WOS:000895788300005
收录类别	PUBMED ; SCOPUS ; SCIE
URL	查看原文
Pubmed记录号	36336009
Scopus记录号	2-s2.0-85141814956
通讯作者地址	[Yan, Zhiwen]Department of Pharmacy,The First Affiliated Hospital of Xiamen University,Xiamen,361003,China ; [Liu, Bili]Department of Pharmacy,The First Affiliated Hospital of Xiamen University,Xiamen,361003,China
scopus学科分类	Pharmacology
引用统计
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/171415
专题	附属第一医院_药学部药学部
通讯作者	Liu, Bili; Yan, Zhiwen
作者单位	1.Department of Pharmacy,The First Affiliated Hospital of Xiamen University,Xiamen,361003,China; 2.Department of Pharmacy,The First Affiliated Hospital of Wenzhou Medical University,Wenzhou,325000,China
推荐引用方式 GB/T 7714	Chen, Fang,Wu, Xiaofeng,Yang, Jiayong,et al. Hippocampal Galectin-3 knockdown alleviates lipopolysaccharide-induced neurotoxicity and cognitive deficits by inhibiting TLR4/NF-кB signaling in aged mice.[J]. European journal of pharmacology,2022,936:175360.
APA	Chen, Fang, Wu, Xiaofeng, Yang, Jiayong, Yu, Xuben, Liu, Bili, & Yan, Zhiwen. (2022). Hippocampal Galectin-3 knockdown alleviates lipopolysaccharide-induced neurotoxicity and cognitive deficits by inhibiting TLR4/NF-кB signaling in aged mice.. European journal of pharmacology, 936, 175360.
MLA	Chen, Fang,et al."Hippocampal Galectin-3 knockdown alleviates lipopolysaccharide-induced neurotoxicity and cognitive deficits by inhibiting TLR4/NF-кB signaling in aged mice.".European journal of pharmacology 936(2022):175360.